Identification of Novel Adipokines Through Proteomic Profiling of Small Extracellular Vesicles Derived from Adipose Tissue.

Adipose tissue is regarded as a true endocrine organ that releases adipokines to regulate distant targets. Besides the well studied secretory adipokines, the adipokines carried by small extracellular vesicles derived from adipose tissue (sEV-AT) have not been completely characterized yet. In this study, we conducted a complementary protein profiling on sEV-AT with Label-free Quantitative Proteomic Analysis (Project accession: PXD013270). A total of 2607 sEV-AT proteins were identified, among which 328 proteins had been annotated as adipokines. 3 undefined adipokine candidates (NPM3, STEAP3, and DAD1) were selected for further validation. These 3 proteins were expressed in both white and brown adipose tissue, upregulated during adipogenic differentiation in both 3T3-L1 cells and adipose-derived stromal/stem cells (ASCs). Expressions of NPM3, DAD1 in sEV-AT were significantly decreased in obese subjects compared with lean controls while obesity could not alter the expression of STEAP3. Our profiling study of the sEV-AT proteins expanded the list of adipokines and highlighted the pivotal role of adipokines specifically carried by sEVs in the regulation of multiple biological processes within adipose tissue.